Cross-sectional study of antimicrobial resistance and ecology in gastrointestinal and oral microbial communities of urban Pakistani adults
Cross-sectional study of antimicrobial resistance and ecology in gastrointestinal and oral microbial communities of urban Pakistani adults
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DOI：
10.1101/2022.11.05.515288
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发表时间：
2022-11
期刊：
影响因子：
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通讯作者：
Maria Batool;C. Keating;Sundus Javed;A. Nasir;M. Muddassar;U. Ijaz
中科院分区：
文献类型：
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作者：
Maria Batool;C. Keating;Sundus Javed;A. Nasir;M. Muddassar;U. Ijaz
抗菌素耐药性（AMR）是影响中低收入国家（LMIC）的最严重的全球公共卫生威胁之一，原因包括缺乏认识、医疗和卫生基础设施不足以及其他环境因素。在这项研究中，我们的目的是将微生物组装和协变量（体重指数，吸烟，抗生素的使用）与肠道微生物组结构联系起来，并将AMR基因的患病率关联起来。方法我们通过16S rRNA基因测序检查了巴基斯坦健康成年人的胃肠道和口腔微生物概况，重点关注不同种族，抗生素使用，饮用水类型，吸烟和其他人口统计学指标。然后，我们利用一套由数值生态学和机器学习驱动的创新统计工具来实现上述目标。结果我们观察到自来水是巴基斯坦队列中AMR发展的主要贡献者。此外，基于零模型程序的微生物生态位宽度分析强调了吸烟者随着年龄增加而出现的异常肠道微生物特征。结论在巴基斯坦，饮用水在AMR传播中起着更重要的作用，而不是其他因素。此外，吸烟和年龄等协变量影响了这个巴基斯坦队列中的人类微生物群落结构。据我们所知，这是首批提供巴基斯坦健康个体微生物组快照的研究之一，并考虑了AMR概况，重点是AMR患病率的潜在来源。巴基斯坦被世界银行归类为低收入和中等收入国家，滥用抗生素的现象普遍，多药耐药性普遍存在。因此，我们必须了解巴基斯坦的抗菌素耐药性和人类微生物组的驱动因素。在一个健康的巴基斯坦队列中，饮用自来水的个体与AMR的相关性几乎高出6倍。因此，饮用水源可能是AMR传播的强大驱动力。局限性一个局限性是使用预测功能概况。然而，考虑到AMR监测的迫切需要，鸟枪宏基因组学对于LMIC来说可能过于昂贵。临床研究相关性我们的研究显示，关键微生物类群与年龄、BMI和性别等协变量之间存在密切关联。此外，我们显示了肠道和口腔群落中存在的特定离群类群之间的相关性，突出了在某些情况下将口腔微生物组用作肠道生态失调的代理的潜在未来可行性。我们应用了分析工具的最新进展，将AMR患病率和人类微生物组组成与年龄、BMI、性别、种族、吸烟状况、抗生素使用和饮用水源等因素联系起来。此外，我们使用零模型表明，微生物群落受到强大的环境压力和扩散限制。我们分析了来自巴基斯坦健康个体的肠道和口腔微生物，发现饮用自来水的人抗生素耐药性的可能性增加。
Background and Aims Antimicrobial resistance (AMR) is one of the most serious global public health threats affecting lower-middle-income countries (LMICs) due to lack of awareness, inadequate healthcare and sanitation infrastructure, plus other environmental factors. In this study, we aimed to link microbial assembly and covariates (body mass index, smoking, use of antibiotics) to gut microbiome structure and correlate AMR gene prevalence. Methods We examined the gastrointestinal and oral microbial profiles of healthy adults in Pakistan through 16S rRNA gene sequencing with a focus on different ethnicities, antibiotic usage, drinking water type, smoking, and other demographic measures. We then utilised a suite of innovative statistical tools, driven by numerical ecology and machine learning, to address the above aims. Results We observed tap water as the main contributor for development of AMR in the Pakistani cohort. In addition, microbial niche breadth analysis based on null modelling procedures highlighted an aberrant gut microbial signature of smokers with increased age. Conclusions Drinking water plays a more important role in AMR spread in Pakistan rather than other factors considered. Moreover, covariates such as smoking, and age impact the human microbial community structure in this Pakistani cohort. To the best of our knowledge, this is one of the first studies that provide a snapshot of the microbiomes of healthy individuals in Pakistan and considers AMR profiles with an emphasis on potential sources of AMR prevalence. Background and Context Pakistan is categorized as a low-and-middle-income country by the World Bank where misuse of antibiotics is widespread, and multidrug resistance is prevalent. Thus, it is imperative that we understand antimicrobial resistance and the drivers of human microbiomes in Pakistan. New Findings In a healthy Pakistani cohort, individuals that consumed Tap Water had almost 6-fold more associations with AMRs. Therefore, drinking water source could be a strong driver in the spread of AMR. Limitations A limitation is the use of predictive functional profiles. However, shotgun metagenomics may be prohibitively costly for LMICs given the urgent need for AMR surveillance. Clinical Research Relevance Our research shows strong associations of key microbial taxa with covariates such as age, BMI, and gender. Additionally, we show correlations between specific outlier taxa that are present both in the gut and oral communities, highlighting potential future feasibility for use of the oral microbiome as a proxy to gut dysbiosis in some cases. Basic Research Relevance We have applied recent advancements in analytical tools to link both AMR prevalence and human microbiome composition with factors such as age, BMI, gender, ethnicity, smoking status, use of antibiotics, and drinking water source. Additionally, we use null modelling to show that the microbial communities are subject to strong environmental pressure and dispersal limitation. Lay Summary We analysed gut and oral microbes from healthy individuals in Pakistan and found that the potential for antibiotic resistance was increased in those who drank tap water.